The goal of this proposed midcareer investigator award is to expand training in multi-disciplinary research focused on the environmental health sciences at the University of Washington. Through collaborations with several ongoing training programs, the candidate, Joel D. Kaufman, MD, MPH, will expand current research efforts and develop a mentoring program with trainees from several relevant disciplines. This program will integrate experimental, epidemiologic, and translational approaches to the role of environmental factors in cardiovascular disease. The proposed research is a continuation of two thematically related projects from Dr. Kaufman's ongoing research program. Both address the thesis that particulate matter air pollution exerts its effect through systemic oxidative stress and inflammation, which in turn results in endothelial dysfunction. The first project studies the effect of diesel exhaust particulate on endothelial function in controlled inhalational exposures, addressing mechanistic hypotheses to understand the role of systemic oxidative stress. The second project is based in an epidemiological study of air pollution effects on cardiovascular disease, and examines the joint and independent effects of acute and chronic pollution exposures on plasma markers of endothelial activation, oxidative stress, and systemic inflammation in a multi-ethnic population-based cohort. The mentorship program builds on Dr. Kaufman's success in multi-disciplinary research, and aims to provide research mentorship in patient-oriented environmental health sciences research to trainees from a wide variety of disciplines. These will include fellows in occupational and environmental medicine, pulmonary medicine, allergy, and cardiology;medical students;and graduate students in epidemiology, toxicology, occupational and environmental hygiene, and environmental engineering. The program will include a research infrastructure (research assistance, data analysis, and biostatistics) and supervised research mentorship. The University of Washington provides an outstanding setting for collaborative training and patient-oriented research in environmental health sciences.